DNAJA2的自我关联平衡调节了它与未折叠的基底蛋白和Hsc70的相互作用
Lorea Velasco-Carneros1,2, Jorge Cuéllar3, Leire Dublang1,2
1Biofisika Institute (CSIC, UPV/EHU), University of the Basque Country, 48940, Leioa, Spain.
Nature communications
|September 5, 2023
概括
人类DNAJA2蛋白形成管状结构,Hsc70可以分解. 这种解离增强了DNAJA2的作用.
科学领域:
- 分子生物学分子生物学
- 蛋白质结构和功能 蛋白质结构和功能
- 伴侣蛋白质 伴侣蛋白质
背景情况:
- J-域蛋白对Hsp70护卫体的特异性和功能至关重要.
- 许多J-域蛋白的精确结构-功能关系仍然不太清楚.
- 人类DNAJA2是一种重要的J-域蛋白质,其结构动力学在很大程度上是未知的.
研究的目的:
- 研究人类DNA的结构和自我组装特性JA2.
- 阐明Hsc70与DNAJA2结构相互作用并调节的机制.
- 了解DNAJA2的结构动态如何影响其与客户端蛋白的相互作用.
主要方法:
- 电子显微镜 (Cryo-EM) 用于结构分析.
- 突变研究以确定涉及自我关联的领域.
- 在体外测试以评估蛋白质-蛋白质相互作用和客户端蛋白质结合.
主要成果:
- DNAJA2可逆地形成高度排序的管状结构.
- Hsc70将这些DNAJA2寡合体解离成二聚体.
- 分离暴露了J域,促进了Hsc70结合和客户端蛋白重塑.
结论:
- DNAJA2自组装成管道调节其与Hsc70和客户端蛋白质的相互作用.
- 管状结构内的J域允许合作性Hsc70结合,以实现高效的客户端恢复.
- DNAJA2的C端域在调节其关联和Hsc70相互作用方面发挥着作用.
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